Scientists Can’t Replicate Gene-Editing Method

Even with the original authors’ vector, the NgAgo technique doesn’t work in others’ hands.

Nov 21, 2016

Kerry Grens

S BURGESS ET AL., PROTEIN & CELL, DOI: 10.1007/s13238-016-0343-9, 2016Researchers continue to fail in reproducing a new gene-editing technique called NgAgo, for Natronobacterium gregoryi Argonaute, an endonuclease. In a report published last week (November 15) in Protein & Cell, scientists from the U.S. and China working independently found no evidence that NgAgo could manipulate DNA sequences.

“Some of us have even sent visiting researchers to [Chunyu] Han’s laboratory but they were not allowed to perform genome editing experiments involving mammalian cells when they were there,” the authors, led by Shawn Burgess of the National Human Genome Research Institute, wrote in their report. “Consequently, none of them returned with any information confirming Han’s data.”

Han and colleagues unveiled NgAgo in May 2016, claiming that the protocol could efficiently edit DNA in human cells with high fidelity. But shortly after, researchers found they couldn’t achieve the same results and began to turn their backs on the technique. In August, Han deposited his expression vector in Addgene, in the “hopes that this will help efforts to reproduce his work,” Nature News reported then.

But even after Burgess’s team used vectors obtained from Addgene and directly from Han’s lab, “no success editing endogenous genomic DNA was achieved,” the group wrote.

As Retraction Watch noted, Nature Biotechnology, which published Han’s paper in May, received tips from several researchers who couldn’t succeed with NgAgo. The publisher is now investigating.

Update (November 30): Nature Biotechnology issued an Expression of Concern this week (November 28) regarding the reproducibility issues surrounding NgAgo. Retraction Watch reported that two of the five authors—Chunyu Han and Xiao Shen—supported the journal’s decision.

Alongside the letter from the editors, Nature Biotechnology also published a study illustrating an independent team’s failed effort to reproduce the technology. “Despite various attempts to optimize NgAgo-mediated genome editing in three of the reported cell lines, no evidence of successful editing of endogenous target sequences was detected,” the authors of the replication attempt reported.

Retraction Watch cited one anonymous source who claimed that the gene-editing method works.